The purpose of the proposed research is to investigate the role of cardiac metabolism in recovery of myocardial mechanical function following ischemia in the isolated working heart. The ability of the heart to utilize substrates and perform work will be determined after various periods of ischemia in order to assess the relationship between $ energy production, high energy phosphate levels and mechanical function. The activities of specific enzymes within the glycolytic and oxidation pathways that account for energy production will be studied. Studies will be conducted to determine factors which modify the activity of these enzymes during ischemia and upon reperfusion of ischemic tissue. Possible factors include: production of inhibitors, loss of enzymes and/or cofactors from the intracellular compartment, and degradation of enzymes by lysosomal proteases. The rates of fatty acid and glucose metabolism will be studied to determine if these processes limit mechanical function of post-ischemic hearts. The studies should yield information on the cellular processes which are involved in precipitating the irreversible phase of myocardial ischemia. The research should also provide a rational basis upon which to devise suitable therapeutic interventions to alleviate cellular damage and aid in recovery of myocardial function in patients receiving coronary bypass surgery.